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1. Lung cancer trends and tumor characteristic changes over 20 years (2000–2020): Results of three French consecutive nationwide prospective cohorts’ studies

Author: Didier Debieuvre, Olivier Molinier, Lionel Falchero, Chrystèle Locher, Dorine Templement-Grangerat, Nicolas Meyer, Hugues Morel, Yannick Duval, Bernard Asselain, Alexia Letierce, Jean Trédaniel, Jean-Bernard Auliac, Olivier Bylicki, Lionel Moreau, Mathieu Fore, Romain Corre, Sébastien Couraud, Alexis Cortot, Faraj Al Freijat, Waad Al Sheikh, Claire Alizon, Karim Amrane, Etienne Auvray, Nicolae Banciu, Alexandra Bedossa, Issam Belhaj, Antoine Belle, Laure Belmont, Kheir Eddine Benmammar, Marie Bernardi, Pascal Beynel, Fréderic Bigot, Acya Bizieux-Thaminy, Anne-Sophie Blanchet-Legens, Philippe Bonnefoy, Soraya Bordier, Anne-Sophie Bravard, Éric Briens, Philippe Brun, Anne-Sophie Bugnet, Laetitia Chablais, Anne-Marie Chiappa, Reda Chikouche, François Christiann, Caroline Clarot, Joelle Courdeau-Labourie, Jacky Crequit, Charles Dayen, Gonzague De chabot, Chantal Decroisette, Stéphanie Dehette, Christian Delafosse, Bertrand Delclaux, Christina Delmas, Pierre Demontrond, Jean-Marc Dot, Cécile Dujon, Patrick Dumont, Christine Dussopt, Fatima Duval, Fethi El Khanjari, Kevin Fouet, Hugues Francois, Yannick Ghalloussi-Tebai, Éric Goarant, Benoît Godbert, François Goupil, Rym Haouachi, Pierre-Alexandre Hauss, Mohamad Jaafar, Baihas Jarjour, Serge Jeandeau, Sylvie Julien, Jean Philippe Kraemer, Pierre Kuntz, Florence Lamotte, Sébastien Larive, Thomas Laurent, Hervé Le Floch, Gwenaëlle Le Garff, Jacques Le Treut, Emmanuelle Lecuyer, Christine Lefoll, Olivier Leleu, Marguerite Lepoulain Doubliez, Virginie Levrat, Sandrine Loutski-Vettese, Edith Maetz, Fanny Magne, Cécile Maincent, Alexa Mairovitz, Catherine Marichy, Nancy Marion, David Marquette, Bénédicte Martignac, Stéphanie Martinez, Clothilde Marty, Philippe Masson, Cyril Maurer, Vincent Meniai, Geoffroy Milliet De Faverges, Isabelle Monnet, Laurent Mosser, Anne-Catherine Neidhardt, David Nunes, Julie Obert, Vanessa Pante, Magalie Paysse, Herve Pegliasco, Jean-Michel Peloni, Christophe Perrin, Lidia Petit, Marjorie Picaud, Julian Pinsolle, Mihai Popa, Laurent Portel, Jean Quieffin, Hong Rabut, Élise Redureau, David Renault, Patrick Aldo Renault, Claudia Rizzo, Maud Russier, Marielle Sabatini, Thierry Saelens, Sophie Schneider, Philippe Slaouti, Luc Stoven, Vincent Tack, Jean-Yves Tavernier, Laurence Thirard, Séverine Thomassin, Marie Tiercin, Jean Tredaniel, Andreea Tudor, Amélie Turlotte, Colette Vincent, and Jérôme Virally
Subjects: Lung cancer, Smoking habits, Real-life, Tumor characteristics, Adenocarcinoma, Non-small-cell lung cancer, Public aspects of medicine, RA1-1270
Abstract: Summary: Background: Long-term changes in lung cancer (LC) patients are difficult to evaluate. We report results from the French KBP-2020 real-life cohort. Methods: KBP-2020 was a prospective cohort that included all patients diagnosed with LC in 2020, in nonacademic public hospital in France. Patient and tumour characteristics were described and compared with similarly designed cohorts in 2000 and 2010. Findings: In 2020, 82 centers included 8,999 patients diagnosed with LC. The proportion of women increased: 34·6% (3114/8999) compared to, 24·3% (1711/7051) and 16·0% (904/5667) in 2010 and 2000 (p
Published: 2022
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2. The Amaryllidaceae Isocarbostyril Narciclasine Induces Apoptosis By Activation of the Death Receptor and/or Mitochondrial Pathways in Cancer Cells But Not in Normal Fibroblasts

Author: Patrick Dumont, Laurent Ingrassia, Sébastien Rouzeau, Fabrice Ribaucour, Stéphanie Thomas, Isabelle Roland, Francis Darro, Florence Lefranc, and Robert Kiss
Subjects: Apoptosis, cancer cells, death receptor pathway, fibroblasts, narciclasine, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Our study has shown that the Amaryllidaceae isocarbostyril narciclasine induces marked apoptosismediated cytotoxic effects in human cancer cells but not in normal fibroblasts by triggering the activation of the initiator caspases of the death receptor pathway (caspase-8 and caspase-10) at least in human MCF-7 breast and PC-3 prostate carcinoma cells. The formation of the Fas and death receptor 4 (DR4) death-inducing signaling complex was clearly evidenced in MCF-7 and PC-3 cancer cells. Caspase-8 was found to interact with Fas and DR4 receptors on narciclasine treatment. However, narciclasine-induced downstream apoptotic pathways in MCF-7 cells diverged from those in PC-3 cells, where caspase-8 directly activated effector caspases such as caspase-3 in the absence of any further release of mitochondrial proapoptotic effectors. In contrast, in MCF-7 cells, the apoptotic process was found to require an amplification step that is mitochondria-dependent, with Bid processing, release of cytochrome c, caspase-9 activation. It is postulated that the high selectivity of narciclasine to cancer cells might be linked, at least in part, to this activation of the death receptor pathway. Normal human fibroblasts appear approximately 250-fold less sensitive to narciclasine, which does not induce apoptosis in these cells probably due to the absence of death receptor pathway activation.
Published: 2007
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3. Cardenolide-Induced Lysosomal Membrane Permeabilization Demonstrates Therapeutic Benefits in Experimental Human Non-Small Cell Lung Cancers

Author: Tatjana Mijatovic, Véronique Mathieu, Jean-François Gaussin, Nancy De Néve, Fabrice Ribaucour, Eric Van Quaquebeke, Patrick Dumont, Francis Darro, and Robert Kiss
Subjects: NSCLCs, cardenolides, antitumor agent, Hsp70, lysosomal membrane permeabilization, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Non-small cell lung cancers (NSCLCs) are the leading cause of cancer deaths in most developed countries. Targeting heat shock protein 70 (Hsp70) expression and function, together with the induction of lysosomal membrane permeabilization (LMP), could overcome the multiple anti-cell death mechanisms evidenced in NSCLCs that are responsible for the failure of currently used chemotherapeutic drugs. Because cardenolides bind to the sodium pump, they affect multiple signaling pathways and thus have a number of marked effects on tumor cell behavior. The aim of the present study was to characterize in vitro and in vivo the antitumor effects of a new cardenolide (UNBS1450) on experimental human NSCLCs. UNBS1450 is a potent source of in vivo antitumor activity in the case of paclitaxeland oxaliplatin-resistant subcutaneous human NCIH727 and orthotopic A549 xenografts in nude mice. In vitro UNBS1450-mediated antitumor activity results from the induction of nonapoptotic cell death. UNBS1450 mediates the decrease of Hsp70 at both mRNA and protein levels, and this is at least partly due to UNBS1450-induced downregulation of NFAT5/ TonEBP (a factor responsible for the transcriptional control of Hsp70). These effects were paralleled by the induction of LMP, as evidenced by acridine orange staining and immunofluorescence analysis for cathepsin B accumulation.
Published: 2006
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4. Stress-Induced Premature Senescence or Stress-Induced Senescence-Like Phenotype: One In Vivo Reality, Two Possible Definitions?

Author: Olivier Toussaint, Patrick Dumont, Jose Remacle, Jean-Francois Dierick, Thierry Pascal, Christophe Frippiat, Joao Pedro Magalhaes, Stephanie Zdanov, and Florence Chainiaux
Subjects: Technology, Medicine, Science
Abstract: No consensus exists so far on the definition of cellular senescence. The narrowest definition of senescence is irreversible growth arrest triggered by telomere shortening counting cell generations (definition 1). Other authors gave an enlarged functional definition encompassing any kind of irreversible arrest of proliferative cell types induced by damaging agents or cell cycle deregulations after overexpression of proto-oncogenes (definition 2). As stress increases, the proportion of cells in “stress-induced premature senescence-like phenotype” according to definition 1 or “stress-induced premature senescence,” according to definition 2, should increase when a culture reaches growth arrest, and the proportion of cells that reached telomere-dependent replicative senescence due to the end-replication problem should decrease. Stress-induced premature senescence-like phenotype and telomere-dependent replicatively senescent cells share basic similarities such as irreversible growth arrest and resistance to apoptosis, which may appear through different pathways. Irreversible growth arrest after exposure to oxidative stress and generation of DNA damage could be as efficient in avoiding immortalisation as “telomere-dependent” replicative senescence. Probabilities are higher that the senescent cells (according to definition 2) appearing in vivo are in stress-induced premature senescence rather than in telomere-dependent replicative senescence. Examples are given suggesting these cells affect in vivo tissue (patho)physiology and aging.
Published: 2002
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5. Transfusions and patient burden in chemotherapy-induced anaemia in France

Author: Patricia K. Corey-Lisle, Marie-Pierre Desrosiers, Helen Collins, Margarita De La Orden, Krista A. Payne, Charles Briac Levaché, and Patrick Dumont
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Objectives: To estimate the patient burden in terms of the time spent on outpatient red blood cell (RBC) transfusions indicated for chemotherapy induced-anaemia (CIA) in patients with cancer in France. Methods: A retrospective chart review of patients with cancer receiving an outpatient RBC transfusion was conducted at seven treatment centres in France. Total treatment time for one transfusion visit per patient was measured as the elapsed time between pre- and post-transfusion vital sign assessment, including time from transfusion start to stop. Elapsed time from haemoglobin (Hb) level testing to transfusion start and from blood draw for compatibility testing to transfusion start were recorded. In addition, estimated travel time and distance to the transfusion centre, and clinical and demographic information were collected. Results: A total of 103 patients [63.1% men; mean age 66.2 years, standard deviation (SD) 11.9] were enrolled in the study (1 August 2010–31 October 2010). The four most frequent diagnoses were lung cancer (31.1%), urological cancer (15.5%), gynecological cancer (14.6%) and gastrointestinal/colorectal cancer (14.6%). Mean elapsed time between prevital and postvital sign assessment was 4.0 h [95% confidence interval (CI) 1.9–6.1], including a mean of 3.4 h (95% CI 2.5–4.2) for the transfusion itself. Hb level testing (mean pre-transfusion Hb level 8.0 g/dl, SD 0.8) and blood draw for compatibility testing were completed in a mean of 28.8 h (95% CI 1.3–56.2) and 9.4 h (95% CI 0–21.4) prior to transfusion respectively. Patients’ one-way mean travel time to the transfusion centre was 32.9 min (95% CI 28.5–37.4) and mean distance travelled was 25.4 km (95% CI 11.6–39.3). Conclusion: In France, CIA treatment with RBC transfusion is a time-consuming activity for patients that includes multiple trips to a medical facility, blood testing and the transfusion procedure itself. This burden is important to consider in the context of optimizing proactive monitoring and planning for supportive oncology care.
Published: 2014
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6. The mucin MUC4 and its membrane partner ErbB2 regulate biological properties of human CAPAN-2 pancreatic cancer cells via different signalling pathways.

Author: Nicolas Jonckheere, Nicolas Skrypek, Johann Merlin, Anne Frédérique Dessein, Patrick Dumont, Emmanuelle Leteurtre, Ann Harris, Jean-Luc Desseyn, Christiane Susini, Frédéric Frénois, and Isabelle Van Seuningen
Subjects: Medicine, Science
Abstract: The mucin MUC4 and its membrane partner the ErbB2 oncogenic receptor are potential interacting partners in human pancreatic tumour development. However, the way they function is still largely unknown. In this work, we aimed to identify the cellular mechanisms and the intracellular signalling pathways under the control of both ErbB2 and MUC4 in a human pancreatic adenocarcinomatous cell line. Using co-immunoprecipitation and GST pull-down, we show that MUC4 and ErbB2 interact in the human pancreatic adenocarcinomatous cell line CAPAN-2 via the EGF domains of MUC4. Stable cell clones were generated in which either MUC4 or ErbB2 were knocked down (KD) by a shRNA approach. Biological properties of these cells were then studied in vitro and in vivo. Our results show that ErbB2-KD cells are more apoptotic and less proliferative (decreased cyclin D1 and increased p27kip1 expression) while migration and invasive properties were not altered. MUC4-KD clones were less proliferative with decreased cyclin D1 expression, G1 cell cycle arrest and altered ErbB2/ErbB3 expression. Their migration properties were reduced whereas invasive properties were increased. Importantly, inhibition of ErbB2 and MUC4 expression did not impair the same signalling pathways (inhibition of MUC4 expression affected the JNK pathway whereas that of ErbB2 altered the MAPK pathway). Finally, ErbB2-KD and MUC4-KD cells showed impaired tumour growth in vivo. Our results show that ErbB2 and MUC4, which interact physically, activate different intracellular signalling pathways to regulate biological properties of CAPAN-2 pancreatic cancer cells.
Published: 2012
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7. Increased adipogenesis in cultured embryonic chondrocytes and in adult bone marrow of dominant negative Erg transgenic mice.

Author: Sébastien Flajollet, Tian V Tian, Ludovic Huot, Nathalie Tomavo, Anne Flourens, Muriel Holder-Espinasse, Marion Le Jeune, Patrick Dumont, David Hot, Frédéric Mallein-Gerin, and Martine Duterque-Coquillaud
Subjects: Medicine, Science
Abstract: In monolayer culture, primary articular chondrocytes have an intrinsic tendency to lose their phenotype during expansion. The molecular events underlying this chondrocyte dedifferentiation are still largely unknown. Several transcription factors are important for chondrocyte differentiation. The Ets transcription factor family may be involved in skeletal development. One family member, the Erg gene, is mainly expressed during cartilage formation. To further investigate the potential role of Erg in the maintenance of the chondrocyte phenotype, we isolated and cultured chondrocytes from the rib cartilage of embryos of transgenic mice that express a dominant negative form of Erg (DN-Erg) during cartilage formation. DN-Erg expression in chondrocytes cultured for up to 20 days did not affect the early dedifferentiation usually observed in cultured chondrocytes. However, lipid droplets accumulated in DN-Erg chondrocytes, suggesting adipocyte emergence. Transcriptomic analysis using a DNA microarray, validated by quantitative RT-PCR, revealed strong differential gene expression, with a decrease in chondrogenesis-related markers and an increase in adipogenesis-related gene expression in cultured DN-Erg chondrocytes. These results indicate that Erg is involved in either maintaining the chondrogenic phenotype in vitro or in cell fate orientation. Along with the in vitro studies, we compared adipocyte presence in wild-type and transgenic mice skeletons. Histological investigations revealed an increase in the number of adipocytes in the bone marrow of adult DN-Erg mice even though no adipocytes were detected in embryonic cartilage or bone. These findings suggest that the Ets transcription factor family may contribute to the homeostatic balance in skeleton cell plasticity.
Published: 2012
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8. Risk factors for early mortality from lung cancer: evolution over the last 20 years in the French nationwide KBP cohorts

Author: Debieuvre, D., Asselain, B., Cortot, A., Couraud, S., Duval, Y., Falchero, L., Locher, C., Meyer, N., Molinier, O., Morel, H., Templement-Grangerat, D., Tredaniel, J., Olivier, Leleu, Caroline, Clarot, Stéphanie, Martinez, Marie, Bernardi, Etienne, Auvray, Julian, Pinsolle, Chantal, Decroisette, Dorine, Templement, Laure, Belmont, Thierry, Saelens, Amélie, Turlotte, Jérôme, Virally, Reda, Chikouche, Marielle, Sabatini, Sophie, Schneider, Jacky, Crequit, Faraj, Al Freijat, Baihas, Jarjour, Rym, Haouachi, Fethi, El Khanjari, Luc, Stoven, Pascal, Beynel, Vincent, Tack, Fatima, Meniai, Yannick, Duval, Hannah, Ghalloussi-Tebai, Claudia, Rizzo, Waad, Al Sheikh, Marguerite, Lepoulain Doubliez, Florence, Lamotte, François, Christiann, Patrick, Dumont, Philippe, Masson, Fréderic, Bigot, Hervé, Le Floch, Issam, Belhaj, Lionel, Moreau, Stéphanie, Dehette, Antoine, Belle, Lidia, Petit, Thomas, Laurent, Sandrine, Loutski-Vettese, Isabelle, Monnet, Jean-Bernard, Auliac, Edith, Maetz, Jean-Yves, Tavernier, Christian, Delafosse, Pierre-Alexandre, Hauss, Colette, Vincent, Mohamad, Jaafar, Jean Philippe, Kraemer, Laetitia, Chablais, Anne-Sophie, Bravard, Philippe, Bonnefoy, Christine, Lefoll, Alexandra, Bedossa, Élise, Redureau, Acya, Bizieux-Thaminy, Virginie, Levrat, Kevin, Fouet, Claire, Alizon, Cécile, Dujon, Hong, Rabut, Mihai, Popa, Jean, Quieffin, Pierre, Demontrond, Olivier, Molinier, François, Goupil, Kheir Eddine, Benmammar, Vanessa, Pante, Laurent, Portel, Anne-Sophie, Blanchet-Legens, Sébastien, Larive, Jacques, Le Treut, Herve, Pegliasco, Chrystèle, Locher, Séverine, Thomassin, Benoît, Godbert, Cécile, Maincent, Christophe, Perrin, Julie, Obert, Cyril, Maurer, David, Renault, Karim, Amrane, Didier, Debieuvre, Geoffroy, Milliet De Faverges, Andreea, Tudor, Maud, Russier, Hugues, Morel, Hugues, Francois, Jean, Tredaniel, Patrick Aldo, Renault, Magalie, Paysse, Anne-Marie, Chiappa, Romain, Corre, Laurent, Mosser, Sylvie, Julien, David, Nunes, Soraya, Bordier, Eric, Briens, Gwenaëlle, Le Garff, Clothilde, Marty, Bénédicte, Martignac, Charles, Dayen, Emmanuelle, Lecuyer, Philippe, Slaouti, Serge, Jeandeau, Christina, Delmas, Eric, Goarant, Marie, Tiercin, Jean-Michel, Peloni, Joelle, Courdeau-Labourie, Nicolae, Banciu, Anne-Sophie, Bugnet, Olivier, Bylicki, Marjorie, Picaud, Laurence, Thirard, Bertrand, Delclaux, Philippe, Brun, Marion, Nancy, David, Marquette, Gonzague, De Chabot, Pierre, Kuntz, Catherine, Marichy, Lionel, Falchero, Christine, Dussopt, Alexa, Mairovitz, Jean-Marc, Dot, Fanny, Magne, Hoang, T.C.T., Bravard, A.-S., Martinez, S., Le Garff, G., Jeandeau, S., Petit, L., Marquette, D., Amrane, K., Demontrond, P., Tiercin, M., Jarjour, B., Turlotte, A., Masson, P., Jaafar, M., and Hauss, P.-A.
Published: 2024
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9. Risk factors for early mortality from lung cancer: evolution over the last 20 years in the French nationwide KBP cohorts

Author: Hoang, T.C.T., primary, Debieuvre, D., additional, Bravard, A.-S., additional, Martinez, S., additional, Le Garff, G., additional, Jeandeau, S., additional, Petit, L., additional, Marquette, D., additional, Amrane, K., additional, Demontrond, P., additional, Tiercin, M., additional, Jarjour, B., additional, Turlotte, A., additional, Masson, P., additional, Jaafar, M., additional, Hauss, P.-A., additional, Morel, H., additional, Asselain, B., additional, Cortot, A., additional, Couraud, S., additional, Duval, Y., additional, Falchero, L., additional, Locher, C., additional, Meyer, N., additional, Molinier, O., additional, Templement-Grangerat, D., additional, Tredaniel, J., additional, Olivier, Leleu, additional, Caroline, Clarot, additional, Stéphanie, Martinez, additional, Marie, Bernardi, additional, Etienne, Auvray, additional, Julian, Pinsolle, additional, Chantal, Decroisette, additional, Dorine, Templement, additional, Laure, Belmont, additional, Thierry, Saelens, additional, Amélie, Turlotte, additional, Jérôme, Virally, additional, Reda, Chikouche, additional, Marielle, Sabatini, additional, Sophie, Schneider, additional, Jacky, Crequit, additional, Faraj, Al Freijat, additional, Baihas, Jarjour, additional, Rym, Haouachi, additional, Fethi, El Khanjari, additional, Luc, Stoven, additional, Pascal, Beynel, additional, Vincent, Tack, additional, Fatima, Meniai, additional, Yannick, Duval, additional, Hannah, Ghalloussi-Tebai, additional, Claudia, Rizzo, additional, Waad, Al Sheikh, additional, Marguerite, Lepoulain Doubliez, additional, Florence, Lamotte, additional, François, Christiann, additional, Patrick, Dumont, additional, Philippe, Masson, additional, Fréderic, Bigot, additional, Hervé, Le Floch, additional, Issam, Belhaj, additional, Lionel, Moreau, additional, Stéphanie, Dehette, additional, Antoine, Belle, additional, Lidia, Petit, additional, Thomas, Laurent, additional, Sandrine, Loutski-Vettese, additional, Isabelle, Monnet, additional, Jean-Bernard, Auliac, additional, Edith, Maetz, additional, Jean-Yves, Tavernier, additional, Christian, Delafosse, additional, Pierre-Alexandre, Hauss, additional, Colette, Vincent, additional, Mohamad, Jaafar, additional, Jean Philippe, Kraemer, additional, Laetitia, Chablais, additional, Anne-Sophie, Bravard, additional, Philippe, Bonnefoy, additional, Christine, Lefoll, additional, Alexandra, Bedossa, additional, Élise, Redureau, additional, Acya, Bizieux-Thaminy, additional, Virginie, Levrat, additional, Kevin, Fouet, additional, Claire, Alizon, additional, Cécile, Dujon, additional, Hong, Rabut, additional, Mihai, Popa, additional, Jean, Quieffin, additional, Pierre, Demontrond, additional, Olivier, Molinier, additional, François, Goupil, additional, Kheir Eddine, Benmammar, additional, Vanessa, Pante, additional, Laurent, Portel, additional, Anne-Sophie, Blanchet-Legens, additional, Sébastien, Larive, additional, Jacques, Le Treut, additional, Herve, Pegliasco, additional, Chrystèle, Locher, additional, Séverine, Thomassin, additional, Benoît, Godbert, additional, Cécile, Maincent, additional, Christophe, Perrin, additional, Julie, Obert, additional, Cyril, Maurer, additional, David, Renault, additional, Karim, Amrane, additional, Didier, Debieuvre, additional, Geoffroy, Milliet De Faverges, additional, Andreea, Tudor, additional, Maud, Russier, additional, Hugues, Morel, additional, Hugues, Francois, additional, Jean, Tredaniel, additional, Patrick Aldo, Renault, additional, Magalie, Paysse, additional, Anne-Marie, Chiappa, additional, Romain, Corre, additional, Laurent, Mosser, additional, Sylvie, Julien, additional, David, Nunes, additional, Soraya, Bordier, additional, Eric, Briens, additional, Gwenaëlle, Le Garff, additional, Clothilde, Marty, additional, Bénédicte, Martignac, additional, Charles, Dayen, additional, Emmanuelle, Lecuyer, additional, Philippe, Slaouti, additional, Serge, Jeandeau, additional, Christina, Delmas, additional, Eric, Goarant, additional, Marie, Tiercin, additional, Jean-Michel, Peloni, additional, Joelle, Courdeau-Labourie, additional, Nicolae, Banciu, additional, Anne-Sophie, Bugnet, additional, Olivier, Bylicki, additional, Marjorie, Picaud, additional, Laurence, Thirard, additional, Bertrand, Delclaux, additional, Philippe, Brun, additional, Marion, Nancy, additional, David, Marquette, additional, Gonzague, De Chabot, additional, Pierre, Kuntz, additional, Catherine, Marichy, additional, Lionel, Falchero, additional, Christine, Dussopt, additional, Alexa, Mairovitz, additional, Jean-Marc, Dot, additional, and Fanny, Magne, additional
Published: 2024
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10. COVID-19 among lung cancer patients: data from a real-life prospective French multicentric study

Author: Olivier, MOLINIER, primary, Julian, PINSOLLE, additional, Acya, BIZIEUX-THAMINY, additional, Sophie, SCHNEIDER, additional, Benoît, GODBERT, additional, Laurent, PORTEL, additional, Hugues, FRANCOIS, additional, Charles, DAYEN, additional, Julie, OBERT, additional, Cécile, DUJON, additional, Patrick, DUMONT, additional, Sylvie, JULIEN, additional, Nicolas, MEYER, additional, Alexia, LETIERCE, additional, Hugues, MOREL, additional, and Didier, DEBIEUVRE, additional
Published: 2024
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11. Luxembourg: Political Developments and Data in 2021

Author: PATRICK DUMONT and RAPHAËL KIES
Published: 2022

12. Supplementary Figure 3 from Loss of a Negative Feedback Loop Involving Pea3 and Cyclin D2 Is Required for Pea3-Induced Migration in Transformed Mammary Epithelial Cells

Author: Anne Chotteau-Lelievre, David Tulasne, Yvan de Launoit, Zoulika Kherrouche, Patrick Dumont, Isabelle Damour, and Franck Ladam
Abstract: PDF file - 42K, Relative luciferase activity measured for the human cyclin d2 promoter. Alignment of the 55 bp Mouse, Rat and Human proximal cyclin d2 promoter region.
Published: 2023

13. Supplementary Figure Legend from Loss of a Negative Feedback Loop Involving Pea3 and Cyclin D2 Is Required for Pea3-Induced Migration in Transformed Mammary Epithelial Cells

Author: Anne Chotteau-Lelievre, David Tulasne, Yvan de Launoit, Zoulika Kherrouche, Patrick Dumont, Isabelle Damour, and Franck Ladam
Abstract: PDF file - 86K
Published: 2023

14. Supplementary Methods from Loss of a Negative Feedback Loop Involving Pea3 and Cyclin D2 Is Required for Pea3-Induced Migration in Transformed Mammary Epithelial Cells

Author: Anne Chotteau-Lelievre, David Tulasne, Yvan de Launoit, Zoulika Kherrouche, Patrick Dumont, Isabelle Damour, and Franck Ladam
Abstract: PDF file - 93K
Published: 2023

15. Supplementary Figure 2 from Loss of a Negative Feedback Loop Involving Pea3 and Cyclin D2 Is Required for Pea3-Induced Migration in Transformed Mammary Epithelial Cells

Author: Anne Chotteau-Lelievre, David Tulasne, Yvan de Launoit, Zoulika Kherrouche, Patrick Dumont, Isabelle Damour, and Franck Ladam
Abstract: PDF file - 283K, Wound healing assay for TAC-V and TAC-Pea3-V cells transfected with ctrl or pea3 siRNAs and treated or not with TGF-β1. Western blot analysis of p27kip1 protein expression.
Published: 2023

16. Data from Loss of a Negative Feedback Loop Involving Pea3 and Cyclin D2 Is Required for Pea3-Induced Migration in Transformed Mammary Epithelial Cells

Author: Anne Chotteau-Lelievre, David Tulasne, Yvan de Launoit, Zoulika Kherrouche, Patrick Dumont, Isabelle Damour, and Franck Ladam
Abstract: The Ets family transcription factor Pea3 (ETV4) is involved in tumorigenesis especially during the metastatic process. Pea3 is known to induce migration and invasion in mammary epithelial cell model systems. However, the molecular pathways regulated by Pea3 are still misunderstood. In the current study, using in vivo and in vitro assays, Pea3 increased the morphogenetic and tumorigenic capacity of mammary epithelial cells by modulating their cell morphology, proliferation, and migration potential. In addition, Pea3 overexpression favored an epithelial–mesenchymal transition (EMT) triggered by TGF-β1. During investigation for molecular events downstream of Pea3, Cyclin D2 (CCND2) was identified as a new Pea3 target gene involved in the control of cellular proliferation and migration, a finding that highlights a new negative regulatory loop between Pea3 and Cyclin D2. Furthermore, Cyclin D2 expression was lost during TGF-β1–induced EMT and Pea3-induced tumorigenesis. Finally, restored Cyclin D2 expression in Pea3-dependent mammary tumorigenic cells decreased cell migration in an opposite manner to Pea3. As such, these data demonstrate that loss of the negative feedback loop between Cyclin D2 and Pea3 contributes to Pea3-induced tumorigenesis.Implications: This study reveals molecular insight into how the Ets family transcription factor Pea3 favors EMT and contributes to tumorigenesis via a negative regulatory loop with Cyclin D2, a new Pea3 target gene. Mol Cancer Res; 11(11); 1412–24. ©2013 AACR.
Published: 2023

17. Supplementary Table 1 from Loss of a Negative Feedback Loop Involving Pea3 and Cyclin D2 Is Required for Pea3-Induced Migration in Transformed Mammary Epithelial Cells

Author: Anne Chotteau-Lelievre, David Tulasne, Yvan de Launoit, Zoulika Kherrouche, Patrick Dumont, Isabelle Damour, and Franck Ladam
Abstract: PDF file - 22K, siRNA sequences used for the cyclin d2 AND pea3 knock-down experiments.
Published: 2023

18. Supplementary Figure 4 from Loss of a Negative Feedback Loop Involving Pea3 and Cyclin D2 Is Required for Pea3-Induced Migration in Transformed Mammary Epithelial Cells

Author: Anne Chotteau-Lelievre, David Tulasne, Yvan de Launoit, Zoulika Kherrouche, Patrick Dumont, Isabelle Damour, and Franck Ladam
Abstract: PDF file - 71K, Western blot analysis of Pea3 protein expression in the MMT and TAC cells. Effect of Pea3 and TGF-β1 on the expression of cell cycle related genes.
Published: 2023

19. Supplementary Figure 1 from Loss of a Negative Feedback Loop Involving Pea3 and Cyclin D2 Is Required for Pea3-Induced Migration in Transformed Mammary Epithelial Cells

Author: Anne Chotteau-Lelievre, David Tulasne, Yvan de Launoit, Zoulika Kherrouche, Patrick Dumont, Isabelle Damour, and Franck Ladam
Abstract: PDF file - 270K, Relative pea3 mRNA and protein expression in TAC-V vs TAC-Pea3-V. Wound healing assay for TAC-V and TAC-Pea3-V cells treated or not with TGF-β1 and with or without Mitomycin C. Apoptosis measurement.
Published: 2023

20. Supplementary Table 2 from Loss of a Negative Feedback Loop Involving Pea3 and Cyclin D2 Is Required for Pea3-Induced Migration in Transformed Mammary Epithelial Cells

Author: Anne Chotteau-Lelievre, David Tulasne, Yvan de Launoit, Zoulika Kherrouche, Patrick Dumont, Isabelle Damour, and Franck Ladam
Abstract: PDF file - 69K, Primers sets used for Q-PCR and ChIP experiments.
Published: 2023

21. Supplementary Table 1 from Colon Cancer Cells Escape 5FU Chemotherapy-Induced Cell Death by Entering Stemness and Quiescence Associated with the c-Yes/YAP Axis

Author: Guillemette Huet, Renata Polakowska, Christian Gespach, Isabelle Van Seuningen, Pierre Formstecher, Lee M. Ellis, Fan Fan, Mohamed Hebbar, François-René Pruvot, Stéphanie Truant, Patrick Dumont, Emmanuelle Leteurtre, Guillaume Millet, Georges Grard, Carole Langlois, Nicolas Skrypek, Laurence Stechly, Didier Monté, Jérôme Vandomme, Anne-Frédérique Dessein, Matthieu Corvaisier, Wassila Igoudjil, and Yasmine Touil
Abstract: PDF file - 55K, Table S1. Expression of cell surface stem cell markers in parental HT29 cells, its 5FUresistant 5F7 and 5F31 clonal derivatives, 5FU- and oxaliplatin-resistant HT29FU and HT29OXA subpopulations.
Published: 2023

22. Supplementary Figure 1 from Colon Cancer Cells Escape 5FU Chemotherapy-Induced Cell Death by Entering Stemness and Quiescence Associated with the c-Yes/YAP Axis

Author: Guillemette Huet, Renata Polakowska, Christian Gespach, Isabelle Van Seuningen, Pierre Formstecher, Lee M. Ellis, Fan Fan, Mohamed Hebbar, François-René Pruvot, Stéphanie Truant, Patrick Dumont, Emmanuelle Leteurtre, Guillaume Millet, Georges Grard, Carole Langlois, Nicolas Skrypek, Laurence Stechly, Didier Monté, Jérôme Vandomme, Anne-Frédérique Dessein, Matthieu Corvaisier, Wassila Igoudjil, and Yasmine Touil
Abstract: PDF file - 309K, Figure S1. Expression of cancer stem cell phenotypes in 5FU-resistant 5F7 and 5F31 clones.
Published: 2023

23. Data from Colon Cancer Cells Escape 5FU Chemotherapy-Induced Cell Death by Entering Stemness and Quiescence Associated with the c-Yes/YAP Axis

Author: Guillemette Huet, Renata Polakowska, Christian Gespach, Isabelle Van Seuningen, Pierre Formstecher, Lee M. Ellis, Fan Fan, Mohamed Hebbar, François-René Pruvot, Stéphanie Truant, Patrick Dumont, Emmanuelle Leteurtre, Guillaume Millet, Georges Grard, Carole Langlois, Nicolas Skrypek, Laurence Stechly, Didier Monté, Jérôme Vandomme, Anne-Frédérique Dessein, Matthieu Corvaisier, Wassila Igoudjil, and Yasmine Touil
Abstract: Purpose: Metastasis and drug resistance are the major limitations in the survival and management of patients with cancer. This study aimed to identify the mechanisms underlying HT29 colon cancer cell chemoresistance acquired after sequential exposure to 5-fluorouracil (5FU), a classical anticancer drug for treatment of epithelial solid tumors. We examined its clinical relevance in a cohort of patients with colon cancer with liver metastases after 5FU-based neoadjuvant chemotherapy and surgery.Results: We show that a clonal 5F31 cell population, resistant to 1 μmol/L 5FU, express a typical cancer stem cell–like phenotype and enter into a reversible quiescent G0 state upon reexposure to higher 5FU concentrations. These quiescent cells overexpressed the tyrosine kinase c-Yes that became activated and membrane-associated upon 5FU exposure. This enhanced signaling pathway induced the dissociation of the Yes/YAP (Yes-associated protein) molecular complex and depleted nuclear YAP levels. Consistently, YES1 silencing decreased nuclear YAP accumulation and induced cellular quiescence in 5F31 cells cultured in 5FU-free medium. Importantly, YES1 and YAP transcript levels were higher in liver metastases of patients with colon cancer after 5FU-based neoadjuvant chemotherapy. Moreover, the YES1 and YAP transcript levels positively correlated with colon cancer relapse and shorter patient survival (P < 0.05 and P < 0.025, respectively).Conclusions: We identified c-Yes and YAP as potential molecular targets to eradicate quiescent cancer cells and dormant micrometastases during 5FU chemotherapy and resistance and as predictive survival markers for colon cancer. Clin Cancer Res; 20(4); 837–46. ©2013 AACR.
Published: 2023

24. Supplementary Table 2 from Colon Cancer Cells Escape 5FU Chemotherapy-Induced Cell Death by Entering Stemness and Quiescence Associated with the c-Yes/YAP Axis

Author: Guillemette Huet, Renata Polakowska, Christian Gespach, Isabelle Van Seuningen, Pierre Formstecher, Lee M. Ellis, Fan Fan, Mohamed Hebbar, François-René Pruvot, Stéphanie Truant, Patrick Dumont, Emmanuelle Leteurtre, Guillaume Millet, Georges Grard, Carole Langlois, Nicolas Skrypek, Laurence Stechly, Didier Monté, Jérôme Vandomme, Anne-Frédérique Dessein, Matthieu Corvaisier, Wassila Igoudjil, and Yasmine Touil
Abstract: PDF file - 54K, Table S2. Effect of 5FU on the cell cycle progression in parental HT29 cells and 5FUresistant HT29 clonal derivatives 5F7 and 5F31.
Published: 2023

25. Supplementary Figure 2 from Colon Cancer Cells Escape 5FU Chemotherapy-Induced Cell Death by Entering Stemness and Quiescence Associated with the c-Yes/YAP Axis

Author: Guillemette Huet, Renata Polakowska, Christian Gespach, Isabelle Van Seuningen, Pierre Formstecher, Lee M. Ellis, Fan Fan, Mohamed Hebbar, François-René Pruvot, Stéphanie Truant, Patrick Dumont, Emmanuelle Leteurtre, Guillaume Millet, Georges Grard, Carole Langlois, Nicolas Skrypek, Laurence Stechly, Didier Monté, Jérôme Vandomme, Anne-Frédérique Dessein, Matthieu Corvaisier, Wassila Igoudjil, and Yasmine Touil
Abstract: PDF file - 202K, Figure S2. Western blot analysis of c-Yes and YAP in human colon cancer cells HT29 and RKO cells treated by oxaliplatin and 5FU.
Published: 2023

26. Supplementary Figure Legend from Colon Cancer Cells Escape 5FU Chemotherapy-Induced Cell Death by Entering Stemness and Quiescence Associated with the c-Yes/YAP Axis

Author: Guillemette Huet, Renata Polakowska, Christian Gespach, Isabelle Van Seuningen, Pierre Formstecher, Lee M. Ellis, Fan Fan, Mohamed Hebbar, François-René Pruvot, Stéphanie Truant, Patrick Dumont, Emmanuelle Leteurtre, Guillaume Millet, Georges Grard, Carole Langlois, Nicolas Skrypek, Laurence Stechly, Didier Monté, Jérôme Vandomme, Anne-Frédérique Dessein, Matthieu Corvaisier, Wassila Igoudjil, and Yasmine Touil
Abstract: PDF file - 50K
Published: 2023

27. Data from Autocrine Induction of Invasive and Metastatic Phenotypes by the MIF-CXCR4 Axis in Drug-Resistant Human Colon Cancer Cells

Author: Guillemette Huet, Christian Gespach, Nicole Porchet, Grégoire Prévost, Yasuhiro Furuichi, Yvan de Launoit, Marie-José Dejonghe, Georges Grard, Rodrigue Dessein, Thécla Lesuffleur, Charles-Henri Lecellier, Mohamed Hebbar, Martin Figeac, François-René Pruvot, Stéphanie Truant, Emmanuelle Leteurtre, Didier Monté, Patrick Dumont, Nicolas Jonckheere, Laurence Stechly, and Anne-Frédérique Dessein
Abstract: Metastasis and drug resistance are major problems in cancer chemotherapy. The purpose of this work was to analyze the molecular mechanisms underlying the invasive potential of drug-resistant colon carcinoma cells. Cellular models included the parental HT-29 cell line and its drug-resistant derivatives selected after chronic treatment with either 5-fluorouracil, methotrexate, doxorubicin, or oxaliplatin. Drug-resistant invasive cells were compared with noninvasive cells using cDNA microarray, quantitative reverse transcription-PCR, flow cytometry, immunoblots, and ELISA. Functional and cellular signaling analyses were undertaken using pharmacologic inhibitors, function-blocking antibodies, and silencing by retrovirus-mediated RNA interference. 5-Fluorouracil– and methotrexate-resistant HT-29 cells expressing an invasive phenotype in collagen type I and a metastatic behavior in immunodeficient mice exhibited high expression of the chemokine receptor CXCR4. Macrophage migration-inhibitory factor (MIF) was identified as the critical autocrine CXCR4 ligand promoting invasion in drug-resistant colon carcinoma HT-29 cells. Silencing of CXCR4 and impairing the MIF-CXCR4 signaling pathways by ISO-1, pAb FL-115, AMD-3100, monoclonal antibody 12G5, and BIM-46187 abolished this aggressive phenotype. Induction of CXCR4 was associated with the upregulation of two genes encoding transcription factors previously shown to control CXCR4 expression (HIF-2α and ASCL2) and maintenance of intestinal stem cells (ASCL2). Enhanced CXCR4 expression was detected in liver metastases resected from patients with colon cancer treated by the standard FOLFOX regimen. Combination therapies targeting the CXCR4-MIF axis could potentially counteract the emergence of the invasive metastatic behavior in clonal derivatives of drug-resistant colon cancer cells. Cancer Res; 70(11); 4644–54. ©2010 AACR.
Published: 2023

28. Supplementary Methods, Figure Legends 1 from Autocrine Induction of Invasive and Metastatic Phenotypes by the MIF-CXCR4 Axis in Drug-Resistant Human Colon Cancer Cells

Author: Guillemette Huet, Christian Gespach, Nicole Porchet, Grégoire Prévost, Yasuhiro Furuichi, Yvan de Launoit, Marie-José Dejonghe, Georges Grard, Rodrigue Dessein, Thécla Lesuffleur, Charles-Henri Lecellier, Mohamed Hebbar, Martin Figeac, François-René Pruvot, Stéphanie Truant, Emmanuelle Leteurtre, Didier Monté, Patrick Dumont, Nicolas Jonckheere, Laurence Stechly, and Anne-Frédérique Dessein
Abstract: Supplementary Methods, Figure Legends 1 from Autocrine Induction of Invasive and Metastatic Phenotypes by the MIF-CXCR4 Axis in Drug-Resistant Human Colon Cancer Cells
Published: 2023

29. Supplementary Table 1 from Autocrine Induction of Invasive and Metastatic Phenotypes by the MIF-CXCR4 Axis in Drug-Resistant Human Colon Cancer Cells

Author: Guillemette Huet, Christian Gespach, Nicole Porchet, Grégoire Prévost, Yasuhiro Furuichi, Yvan de Launoit, Marie-José Dejonghe, Georges Grard, Rodrigue Dessein, Thécla Lesuffleur, Charles-Henri Lecellier, Mohamed Hebbar, Martin Figeac, François-René Pruvot, Stéphanie Truant, Emmanuelle Leteurtre, Didier Monté, Patrick Dumont, Nicolas Jonckheere, Laurence Stechly, and Anne-Frédérique Dessein
Abstract: Supplementary Table 1 from Autocrine Induction of Invasive and Metastatic Phenotypes by the MIF-CXCR4 Axis in Drug-Resistant Human Colon Cancer Cells
Published: 2023

30. Supplementary Figure 1 from Autocrine Induction of Invasive and Metastatic Phenotypes by the MIF-CXCR4 Axis in Drug-Resistant Human Colon Cancer Cells

Author: Guillemette Huet, Christian Gespach, Nicole Porchet, Grégoire Prévost, Yasuhiro Furuichi, Yvan de Launoit, Marie-José Dejonghe, Georges Grard, Rodrigue Dessein, Thécla Lesuffleur, Charles-Henri Lecellier, Mohamed Hebbar, Martin Figeac, François-René Pruvot, Stéphanie Truant, Emmanuelle Leteurtre, Didier Monté, Patrick Dumont, Nicolas Jonckheere, Laurence Stechly, and Anne-Frédérique Dessein
Abstract: Supplementary Figure 1 from Autocrine Induction of Invasive and Metastatic Phenotypes by the MIF-CXCR4 Axis in Drug-Resistant Human Colon Cancer Cells
Published: 2023

31. Tailoring maintenance chemotherapy upon response to induction chemotherapy as compared with pemetrexed continuation maintenance in advanced non-squamous NSCLC patients: Results of the IFCT-GFPC-1101 multicenter randomized phase III trial

Author: Alexis B. Cortot, Didier Debieuvre, L. Moreau, Radj Gervais, Jacques Margery, Julien Mazieres, Olivier Molinier, Michel Poudenx, Alexandra Langlais, Nicolas Girard, Patrick Dumont, Gérard Zalcman, Franck Morin, Virginie Westeel, Pierre-Jean Souquet, Eric Pichon, Fabrice Barlesi, Maurice Pérol, Jérôme Dauba, Jacques Cadranel, Clarisse Audigier-Valette, and Denis Moro-Sibilot
Subjects: Adult, Pulmonary and Respiratory Medicine, Oncology, Cancer Research, medicine.medical_specialty, Lung Neoplasms, Adolescent, Pemetrexed, Maintenance Chemotherapy, Young Adult, Carcinoma, Non-Small-Cell Lung, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Aged, Maintenance chemotherapy, business.industry, Induction chemotherapy, Induction Chemotherapy, Middle Aged, Treatment Outcome, Non squamous, Cisplatin, business, medicine.drug
Abstract: Benefit from maintenance in advanced non-squamous non-small cell lung cancer (NS-NSCLC) might favor switch maintenance after disease stabilization (SD) and continuation after objective response (OR). This trial assessed a maintenance strategy conditioned by response to cisplatin-gemcitabine (CG) with G continuation for patients with OR or switch to pemetrexed (P) for patients with SD as compared with a control arm based on the Paramount regimen.Eligibility criteria: age 18-70 years, ECOG PS 0-1, untreated stage IV NS-NSCLC without EGFR or ALK alteration, ineligibility to bevacizumab. Patients were randomized 1:1 to receive either CG (4 cycles) followed by G maintenance in case of OR followed by P at progression, or switch to P for patients with SD, or 4 cycles of CP followed by P (control arm). Primary endpoint: overall Survival.Between 2012 and 2016, 932 patients were randomized (CG: 467, CP: 465) with well-balanced characteristics. 257 patients (56.7%) in the CG arm received maintenance (G: 142, P: 113) versus 277 patients (59.7%) in the CP arm. Median number of maintenance cycles was 5 for G and P (CG induction) and 4 for P (CP induction). OS adjusted HR was 0.97 (95% CI 0.84, 1.13; p = 0.71) with a median of 10.9 months (CG) versus 10.4 (CP). HR for PFS was 0.95 (95% CI 0.83, 1.09; p = 0.45) with a median of 4.8 months for CG versus 4.5 for CP. Safety profile was as expected.Adapting maintenance strategy according to response to induction chemotherapy does not improve patient outcome.NCT01631136.
Published: 2022

32. A comparison of two views on the European Commission: engine of integration and conduit of national interests

Author: Patrick Dumont and Robert Thomson
Subjects: Politics, Public Administration, Sociology and Political Science, Political science, Law, European integration, Nationality, European commission, Allegiance, Commission
Abstract: The conventional view of the Commission is that it is above the fray of national politics, and that Commissioners have allegiance to pan-European interests. However, research indicates that the Com...
Published: 2021

33. Party Politics in Luxembourg

Author: Patrick Dumont, Raphaël Kies, and Dan Schmit
Published: 2022

34. Party Politics in European Microstates

Author: Patrick Dumont
Published: 2022

35. Party Politics in European Microstates

Author: Fernando Casal Bértoa and Patrick Dumont
Published: 2022

36. Luxembourg: Political Developments and Data in 2020

Author: Raphaël Kies, Dan Schmit, and Patrick Dumont
Subjects: Politics, Political economy, Political science
Published: 2021

37. Chest CT scan plus x-ray versus chest x-ray for the follow-up of completely resected non-small-cell lung cancer (IFCT-0302): a multicentre, open-label, randomised, phase 3 trial

Author: Virginie Westeel, Pascal Foucher, Arnaud Scherpereel, Jean Domas, Philippe Girard, Jean Trédaniel, Marie Wislez, Patrick Dumont, Elisabeth Quoix, Olivier Raffy, Denis Braun, Marc Derollez, François Goupil, Jacques Hermann, Etienne Devin, Hubert Barbieux, Eric Pichon, Didier Debieuvre, Gervais Ozenne, Jean-François Muir, Stéphanie Dehette, Jérôme Virally, Michel Grivaux, François Lebargy, Pierre-Jean Souquet, Faraj Al Freijat, Nicolas Girard, Emmanuel Courau, Reza Azarian, Michel Farny, Jean-Paul Duhamel, Alexandra Langlais, Franck Morin, Bernard Milleron, Gérard Zalcman, and Fabrice Barlesi
Subjects: Lung Neoplasms, Oncology, Carcinoma, Non-Small-Cell Lung, X-Rays, Antineoplastic Combined Chemotherapy Protocols, Humans, Tomography, X-Ray Computed, Early Detection of Cancer, Follow-Up Studies
Abstract: Even after resection of early-stage non-small-cell lung cancer (NSCLC), patients have a high risk of developing recurrence and second primary lung cancer. We aimed to assess efficacy of a follow-up approach including clinic visits, chest x-rays, chest CT scans, and fibre-optic bronchoscopy versus clinical visits and chest x-rays after surgery for resectable NSCLC.In this multicentre, open-label, randomised, phase 3 trial (IFCT-0302), patients aged 18 years or older and after complete resection of pathological stage I-IIIA NSCLC according to the sixth edition of the TNM classification were enrolled within 8 weeks of resection from 122 hospitals and tertiary centres in France. Patients were randomly assigned (1:1) to CT-based follow-up (clinic visits, chest x-rays, thoraco-abdominal CT scans, and fibre-optic bronchoscopy for non-adenocarcinoma histology) or minimal follow-up (visits and chest x-rays) after surgery for NSCLC, by means of a computer-generated sequence using the minimisation method. Procedures were repeated every 6 months for the first 2 years and yearly until 5 years. The primary endpoint was overall survival analysed in the intention-to-treat population. Secondary endpoints, also analysed in the intention-to-treat population, included disease-free survival. This trial is registered with ClinicalTrials.gov, NCT00198341, and is active, but not enrolling.Between Jan 3, 2005, and Nov 30, 2012, 1775 patients were enrolled and randomly assigned to a follow-up group (888 patients to the minimal follow-up group; 887 patients to the CT-based follow-up group). Median overall survival was not significantly different between follow-up groups (8·5 years [95% CI 7·4-9·6] in the minimal follow-up group vs 10·3 years [8·1-not reached] in the CT-based follow-up group; adjusted hazard ratio [HR] 0·95, 95% CI 0·83-1·10; log-rank p=0·49). Disease-free survival was not significantly different between follow-up groups (median not reached [95% CI not estimable-not estimable] in the minimal follow-up group vs 4·9 [4·3-not reached] in the CT-based follow-up group; adjusted HR 1·14, 95% CI 0·99-1·30; log-rank p=0·063). Recurrence was detected in 246 (27·7%) of 888 patients in the minimal follow-up group and in 289 (32·6%) patients of 887 in the CT-based follow-up group. Second primary lung cancer was diagnosed in 27 (3·0%) patients in the minimal follow-up group and 40 patients (4·5%) in the CT-based follow-up group. No serious adverse events related to the trial procedures were reported.The addition of thoracic CT scans during follow-up, which included clinic visits and chest x-rays after surgery, did not result in longer survival among patients with NSCLC. However, it did enable the detection of more cases of early recurrence and second primary lung cancer, which are more amenable to curative-intent treatment, supporting the use of CT-based follow-up, especially in countries where lung cancer screening is already implemented, alongside with other supportive measures.French Health Ministry, French National Cancer Institute, Weisbrem-Benenson Foundation, La Ligue Nationale Contre Le Cancer, and Lilly Oncology.For the French translation of the abstract see Supplementary Materials section.
Published: 2022

38. Switch maintenance chemotherapy versus observation after carboplatin and weekly paclitaxel doublet chemotherapy in elderly patients with advanced non–small cell lung cancer: IFCT-1201 MODEL trial

Author: Didier Debieuvre, Pierre-Jean Souquet, Jean-Louis Pujol, Jérôme Dauba, Jeannick Madelaine, Olivier Molinier, J. Otto, Jacques Le Treut, Fabrice Barlesi, Elisabeth Quoix, Patrick Aldo Renault, Eric Pichon, Alexandra Langlais, Virginie Westeel, L. Moreau, Franck Morin, Jacques Margery, Clarisse Audigier-Valette, Armelle Lavolé, Patrick Dumont, Denis Moro-Sibilot, CHU Strasbourg, Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Le Mans (CH Le Mans), Service de Pneumologie, oncologie thoracique et allergologie respiratoire [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier du Pays d'Aix, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Layné, Université Côte d'Azur (UCA), Hôpital pasteur [Colmar], Service de pneumologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier de Chauny, Partenaires INRAE, Hôpital d'instruction des Armées Percy, Service de Santé des Armées, Groupe hospitalier de la région de Mulhouse Sud-Alsace (GHRMSA), Centre hospitalier de Pau, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Intergroupe Francophone de Cancérologie Thoracique [Paris] (IFCT), Intergroupe Francophone de Cancérologie thoracique, CHU Grenoble, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service de Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: Male, 0301 basic medicine, Oncology, Cancer Research, Lung Neoplasms, Time Factors, medicine.medical_treatment, NSCLC, Deoxycytidine, Carboplatin, chemistry.chemical_compound, Elderly, MESH: Aged, 80 and over, 0302 clinical medicine, Maintenance therapy, MESH: Progression-Free Survival, MESH: Carboplatin, Carcinoma, Non-Small-Cell Lung, Antineoplastic Combined Chemotherapy Protocols, Aged, 80 and over, MESH: Aged, MESH: Antimetabolites, Antineoplastic, Drug Substitution, Age Factors, MESH: Neoplasm Staging, Progression-Free Survival, 3. Good health, MESH: Maintenance Chemotherapy, MESH: Antineoplastic Combined Chemotherapy Protocols, Pemetrexed, 030220 oncology & carcinogenesis, Disease Progression, Female, MESH: Disease Progression, France, medicine.drug, Antimetabolites, Antineoplastic, medicine.medical_specialty, Paclitaxel, Maintenance, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Drug Administration Schedule, Drug Administration Schedule, Maintenance Chemotherapy, 03 medical and health sciences, Internal medicine, medicine, Carcinoma, Humans, Chemotherapy, MESH: Paclitaxel, MESH: Pemetrexed, Lung cancer, Aged, Neoplasm Staging, MESH: Age Factors, MESH: Humans, Performance status, business.industry, MESH: Time Factors, MESH: Deoxycytidine, medicine.disease, Gemcitabine, MESH: Drug Substitution, MESH: Male, MESH: Lung Neoplasms, MESH: France, 030104 developmental biology, chemistry, business, MESH: Female, MESH: Carcinoma, Non-Small-Cell Lung
Abstract: International audience; Purpose: Maintenance chemotherapy is a reasonable choice for patients with metastatic non-small cell lung carcinoma (NSCLC) not progressing after induction therapy with a platinum-based doublet. Nevertheless, there have been no studies dedicated to elderly patients.Patients and methods: We conducted a randomised trial in patients aged 70-89 years, with advanced NSCLC (with neither EGFR mutation nor ALK rearrangement), who had not progressed after four cycles of monthly carboplatin and weekly paclitaxel in order to compare maintenance with either pemetrexed (500 mg/m2 d1, 22) in patients with non-squamous cell carcinoma or gemcitabine (1,150 mg/m2 d1, 8, 22) in squamous cell carcinoma to simple observation. The patients were required to have a performance status (PS) 0-2, mini-mental score >23, and creatinine clearance ≥45 mL/min. The primary end-point was overall survival (OS).Results: 632 patients were enrolled from May 2013 to October 2016. Of the 328 (52.3%) patients randomised after induction therapy, 166 patients were assigned to the observation arm, versus 162 to the switch maintenance arm, 119 of whom received pemetrexed and 43 gemcitabine. The median OS from randomisation was 14.1 months (95% confidence interval [CI]: 12.0-17.0) in the observation arm and 14 months (95% CI: 10.9-16.9) in the maintenance arm (p = 0.72). The median progression-free survival (PFS) from randomisation was 2.7 months (95% CI: 2.6-3.1) in the observation arm versus 5.7 months (95% CI: 4.8-7.1) in the maintenance arm (p < 0.001).Conclusion: Switch maintenance therapy significantly prolonged PFS but not OS and, thus, should not be proposed to elderly patients with advanced NSCLC.
Published: 2020

39. Luxembourg: Political Developments and Data in 2019

Author: Patrick Dumont, Raphaël Kies, and Dan Schmit
Subjects: Politics, Political science, Political economy
Published: 2020

40. Somatic profile in lung cancers is associated to reproductive factors in never-smokers women: Results from the IFCT-1002 BioCAST study

Author: Bruno Coudert, Bénédicte Mastroianni, P. Foucher, Séverine Fraboulet, Adrien Dixmier, Julien Mazieres, Michel Vincent, Eric Dansin, Eric Pichon, M. Locatelli-Sanchez, Jacques Cadranel, Sébastien Couraud, N. Baize, Isabelle Monnet, Franck Morin, Catherine Dubos-Arvis, P. Missy, C. Fontaine-Delaruelle, Patrick Dumont, Denis Moro-Sibilot, Hôpital Larrey [Toulouse], CHU Toulouse [Toulouse], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Service de pneumologie, Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Férération d'oncologie thoracique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université d'Angers (UA), INSAVALOR, Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA), Intergroupe Francophone de Cancérologie Thoracique [Paris] (IFCT), Intergroupe Francophone de Cancérologie thoracique, Unité pneumologie et oncologie thoracique [CHU Tenon], CHU Tenon [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Lung Neoplasms, Multivariate analysis, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, Cohort Studies, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, 0302 clinical medicine, Gene Frequency, Risk Factors, Internal medicine, Humans, Medicine, Anaplastic Lymphoma Kinase, Lung cancer, Reproductive History, Aged, 030304 developmental biology, Aged, 80 and over, 0303 health sciences, Smokers, Lung, business.industry, Oncogenes, Middle Aged, medicine.disease, 3. Good health, ErbB Receptors, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cohort, Menarche, Biomarker (medicine), Female, Observational study, France, business, Hormone
Abstract: Background Lung cancer in women is on the rise, with a higher proportion occurring in lifelong never-smokers. Lung cancer in never-smokers (LCINS) exhibits a high frequency of driver oncogene alterations. In this study, we aimed to investigate whether exposure to reproductive factors in women with LCINS may modulate the molecular pattern. Methods All newly diagnosed LCINSs were included in a prospective, observational study (IFCT-1002 BioCAST). Each patient responded to a questionnaire including reproductive factors. Biomarker test results were also collected. Results Two hundred and sixty women were included in this analysis, and 166 alterations were characterized. EGFR mutation frequency proved greater among patients with late menarche (74% in age > 14 vs. 40% and 41% for 12–14 and ≤ 12 years, respectively; P = 0.020) and tended to decrease with increasingly late age at menopause. In multivariate analysis, EGFR mutation frequency increased by 23% per increment of 1 year of age at menarche (P = 0.048), and by 9% for each year at age at first birth (P = 0.035). ALK alteration frequency was greater in women with high parity (50% in ≥ 5 vs. 12% and 7% for 1–4 and nulliparity, respectively; P = 0.021). Conclusion In a cohort of women LCINSs, female hormonal factors appear to impact molecular pattern.
Published: 2020

41. Luxembourg

Author: Dan Schmit, Raphaël Kies, and Patrick Dumont
Published: 2022

42. Coalition Formation in Belgium

Author: Patrick Dumont and Lieven De Winter
Published: 2021

43. Belgium: From Highly Constrained and Complex Bargaining Settings to Paralysis?

Author: Patrick Dumont and Lieven De Winter
Subjects: medicine.medical_specialty, Physical medicine and rehabilitation, medicine, Paralysis, Economics, medicine.symptom
Abstract: While Belgium undoubtedly had the most complex coalition bargaining system in Western Europe during the period 1946–1999, it has become much more difficult for parties to form federal governments ever since. Contrary to a number of European countries, government formation complexity did not peak due the emergence of brand-new parties, nor of any new cleavage. Rather, in Belgium the main ingredients pre-existed: party system fragmentation—which was already high since unitary parties had split along linguistic lines—skyrocketed as the mainstream parties around which post-war coalitions were formed further declined in size, confronting some (in)formateurs with up to ten coalitionable parties. Their task has been further complicated by the growing saliency and Flemish radicalization of the community cleavage which led to the rise of the independentist N-VA, whose positions remain unacceptable for any French-speaking party. As a result, Belgium has often been left without a fully empowered government, the partisan composition of coalitions broke away from previous patterns, and the coalition compromise model, which was already solidly entrenched in the consociational norms and practices since the 1960s, was further elaborated. Coalition partners keep tabs on each other through compromise mechanisms and policy-monitoring devices such as long and detailed coalition agreements, the enhanced role of the inner cabinet composed of the PM and the vice-PMs of each coalition party, and strictly enforced coalition discipline in legislative matters. But, given the increasingly unbridgeable divides between Flemish- and French-speaking parties, the deadlock observed could well lead to the demise of Belgium.
Published: 2021

44. Luxembourg: Political developments and data in 2018

Author: Dan Schmit, Raphaël Kies, and Patrick Dumont
Subjects: Politics, Political economy, Political science
Published: 2019

45. Risk factors for Coronavirus Disease 2019 (COVID-19) severity and mortality among solid cancer patients and impact of the disease on anticancer treatment: A French nationwide cohort study (GCO-002 CACOVID-19)

Author: Astrid Lièvre, Anthony Turpin, Isabelle Ray-Coquard, Karine Le Malicot, Juliette Thariat, Guido Ahle, Cindy Neuzillet, Xavier Paoletti, Olivier Bouché, Kais Aldabbagh, Pierre Michel, Didier Debieuvre, Anthony Canellas, Marie Wislez, Lucie Laurent, May Mabro, Raphael Colle, Anne-Claire Hardy-Bessard, Laura Mansi, Emeline Colomba, Jean Bourhis, Philippe Gorphe, Yoann Pointreau, Ahmed Idbaih, Renata Ursu, Anna Luisa Di Stefano, Gérard Zalcman, Thomas Aparicio, Solenne Moulin, Olivier Leleu, Sylvie Leparree, Henri Goasdoue, Christine Piprot, Gerald Tourneur, Vincent Bayart, Delphine Lignier, Emma Lachaier, Marwa Khamari, Alexandre Coutte, Nicolas Siembida, Aline Houessinon, Jean Marc Regimbeau, Bruno Chauffert, Aurélie Moreira, Vincent Hautefeuille, Christine Hee, Mathieu Boone, Céline Bihan, Emilie Chive, Stéphane Poulet-Potriquier, Rachida Fahem, Dominique Luet, Guillaume Roquin, Carole Vitellius, Nathanaëlle Cornet-Trichereau, François-Xavier Caroli-Bosc, Anne Thirot-Bidault, Stanislas Ropert, Julie Gachet - Masson, Mélanie Dehais, Gwen-Ael L'helgoualc'h, Ibrahim Ali-Mahamadou, Safia Talfi, Laure Belmont, Dieudonné Kilendo, Nasro Benrezzak, Emeline Dubief, Guillaume Conroy, Laurence Delique, Maud Basso, Isabelle Pons, Karine Salignon, Anne-Laure Villing, Emmanuelle Mougenot, Cassandra Porebski, Asma Guiatni, Nicolas Cloarec, Laurent Mineur, Marie Bouchaud, Céleste David, Annie Peytier, Thomas Greletty, Franck Audemar, Emanuelle Vignes, Floriane Minne, Guillaume Goldzak, Fabienne Huysman, Fayçal Hocine, Zaher Lakkis, Guillaume Meynard, Hamadi Almotlak, Elodie Klajer, Xu-Shan Sun, Julie Wasselin, Pascale Catala, Claire Mazuy, Hélène Vandamme, Jean-Briac Prevost, Aurélie Fadin, Laurent Basson, Jean-Baptiste Huguet, Emmanuelle Dos Santos, Bérangère Jany, Alain Saad, Frédéric Goutorbe, Eric Oziol, Mohamed Ramdani, Ouafae Kadiri, Delphine Garbay, Clotilde Huet, Etienne Giroux Leprieur, Wen Teng, Justine Monvoisin, Patrick Arnaud Coffin, Sylvie Roux, Hubert Orfeuvre, Mélanie Chagros, Didier Pillon, Agathe Rassoul, Pierre Guillaume Poureau, Cécile Novello, François Ducray, Cécile Trouba, Vianney Bastit, Emmanuel Babin, Vincent Leon, Anne-Catherine Courtecuisse, Julie Vambre, Vincent Tack, Christophe Desauw, Fatima Meniai, Christina Peres, Aurélie Esparcieux, Hervé Perrier, Nathalie Doux, Régis Kaphan, Bertrand Roques, Christine Rebischung, Dominique Mille, Gaëlle Fernandes, Naceur Abdelli, Natacha Jousset, Pierre Combe, Eric Jonveaux, Patrick Dumont, Marc Kanaan, Corinne Berthelot Gras, Valérie Panis, Laure Kaluzinski, Marjolène Venant-Valery, You-Heng Lam, Laura Vallee, Frédéric Riviere, Muriel Durand, Dihya Benghadid, Emilie Villeneuve, Olivia Hentic Dhome, Zedjiga Bounouar, Louis De Mestier, Jacqueline Dubois, Magali Eyriey, Lionel Moreau, Dib Baihas, Kaïs Aldabbagh, Dominique Degriffolet, Virginie Sebbagh, Jean-Christophe Seghezzi, Marion Lozach-Brugirard, Julie Mandrou, Loubna Mavier, Florence Hennetier, Jean-Philippe Wagner, Elisabeth Carola, Karthiga Chandirakumaran, Sandrine Loutski, Isabelle Cojean-Zelek, Amina Bouras, Sandrine Lacour, Fahem Froura, Hadjer Ben Nadji, Sophie Cattelain, Franck Darloy, Geneviève Jolimoy Boilleau, Cyrielle Maissiat, Ariane Darut-Jouve, Véronique Lorgis, Ikram Charifi-Alaoui, François Ghiringhelli, Antoine Drouillard, Marie Chaix, Sylvain Manfredi, Côme Lepage, Alice Gagnaire, Marianne Latournerie, Sofia jourdan, Nora Perrot, Mireille folia, Anne Minello, Jean-Louis Jouve, Marielle Fery, Alain Landau, Diane Evrard, Bruno Valenza, Jean-François Paitel, Laetitia Chablais, Thomas Kreitmann, Laurence Lancry-Lecomte, Adrien Monard, Eve Faugeras, Paul Boucheret, Cécile Glommeau, Christine Tchikladze, Claire Garnier Tixidre, Jérôme Long, Manel Zaidi, Véronique Delabarre, Juliette Meyzenc, Loïc Ferrand, Denis Moro-Sibilot, Paul Bouheret, Cécile Leyronnas, Camille Herve, Audrey Thoor, Emanuelle Jacquet, Gaël Roth, Videsheka Madapathage-Senanyake, Peggy Chupeau, Elsa Bieber, Maud Rosso, Isabelle Lepage, Frank Priou, Margot Laly, Sylvie Aprelon, Natacha Sobolak, Helen Homokos, Fabienne Watelle, Alice Pham-Becker, Géraldine Lauridant, Charlotte Dujardin, Etienne Lenglin, Aimée Nienguet Tsota, Sophie Dominguez, Alexandra Forestier, Franck Nouvel, Justine Lerooy, Céline Ratajczak, Olivier Romano, Dorothéee Brzyski, Aurélien Barriere, Dominique Genet, Julien Tisse, Xavier Zasadny, Adeline Grelet, Amélie Hennion-Imbault, Eglantine Haustraete, Samy Louafi, Manal Awad, Younes Zekri, Caroline Cheneau, Nolwen Leissen, Joëlle Egreteau, Alexandra Breant, Matthieu Sarabi, Stéphanie Labonne, Julien Forestier, Céline Leclercq, Florence Prunier-Bossion, Isabelle Ray Coquard, Marielle Guillet, Aurélie Theillaumas, Emilie Prome, Thomas Walter, Pierre Philouze, Melody Lawo, Solène De Talhouet, Johanne Beuvelot, Yann Molin, Marie Bellecoste Martin, Maud Saussereau, Lauren Agnelli, Nicolas Fakhry, Christophe Laplace, Emmanuelle Norguet Monnereau, Céline Boucard, Kahina Djenad, Catherine Fontaine, Jean-François Seitz, Laétitia Dahan, Julie Sigrand, Muriel Duluc, Christophe Locher, Marjory Fleury, Ange Brou Marie, Ramdane Berkane, Séverine Poupblanc, Dominique Auby, Daniela Petran, Patrick Texereau, Elodie Guerineau, Morgan Andre, Linda Mahjoubi, Fanny Sarrazin, Sonia Jeanson, Anthony Gschwend, Virginie Birr, Mathieu Fore, Monique Noirclerc, Sihem Dahou, Dominique Spaeth, Mélanie Lambotin, Thomas Lelu, Benjamin Linot, Nathalie Hugon, Dominique Rousseau, Hélène Castanie, Carole Lenne, Alain Lortholary, Anatole Cessot, Messaouda Merzoug, Cécile Naudin, Jean-Michel Vannetzel, Ghina Aziz, Yacine Hadj Arab, Stéphanie Pernes, Isabelle Roche-Lachaise, Frédéric Fiteni, Hadjer Yahiaoui, Gwendoline Marel Lopez, Jeanne Oddoz, Fabienne Peira, Olivier Michel, Jérôme Meunier, Brahim Ouahrani, Antoine Roger, Sonia Branco, Van Nguyen, Mathilde Gisselbrecht, Ghania Hammad, Pierre Mordant, Magda Stroksztejn, Marc Pocard, Luc Nlo Meyengue, Emmanuelle Sacco, Sophie Simon Anne, Elizabeth Fabre-Guillevin, Marine Slim, Aziz Zaanan, Jacques Cadranel, Johan Pluvy, Rénata Ursu, Amyrath Geraldo, Rime Lihi, Maryline Vo, Zohra Brouk, Raphaël Colle, Mostefa Bennamoun, Fabrice Lacan, Christophe Louvet, Soraya Mebarki, Marianne Veyri, Elena Paillaud, Christelle Lucas, Olivier Dubreuil, Jamila Lyamani, Hanane Agguini, Emilie Soularue, Clément Jourdaine, Benjamin Verillaud, Hakima Herzine, Eric Raymond, Nathalie Mathiot, Lola Jade Palmieri, Christian Epanya, Julien Taieb, Eliane Bertrand, Gaël Goujon, Céline Namour, Benoit Gazeau, Biljana Zafirova, Haitham Mirghani, Catherine Belin, Kahina Belkhir, Myriam Gharib, Aurore Vozy, Karim Amrane, Jean-Philippe Spano, Johanna Wassermann, Loic Feuvret, Jean-Baptiste Bachet, Sara Philonenko, Laetitia Guillot, Marion Zabbe, Stéphanie Gibiat, Camille Baylot, Aude Jouinot, Nicolas Leduc, Sabine Vieillot, Laurie James, Camille Ducerf, Jean-Frédéric Blanc, Claire Falandry Leger, Virginie Wautot, Marion Chauvenet, Aude Vincent, David Tougeron, Sandrine Goulvent, Etienne Suc, Anne-Pascale Laurenty, Eric Marquis, Margaux Bonnaire, Maxime Dewolf, Esteban Brenet, Delphine Billard, Claude-Fabien Litre, Antoine Dumazet, Damien Botsen, Marion Vazel, Claire Carlier, David Bonnerave, Charles Marchand-Crety, Olivier Bouche, Patricia Fosse, David Sefrioui, Sarah Watson, Fatah Torche, Thierry Muron, Stéphane Natur, Romain Desgrippes, Véronique Bihel, François-Régis Ferrand, Caroline Leiterer, Julie Lavole, Claire Moquet, Nathalie Pressoir, Catherine Dziukala, Catherine Ligeza Poisson, Abdelhalim Naji, Nicolas Williet, Jean-Marc Phelip, Fabrice Di Palma, Amina Kherrour Mehdi, Julien Langrand-Escure, Pierre Fournel, Grégoire Pigne, Léa Saban-Roche, Nicolas Magne, Cécile Vassal, Jean-Philippe Jacquin, Carole Ramirez, Alexis Vallard, Olivier Collard, Romain Rivoirard, Ivan Graber, Stéphanie Trager Maury, Elodie Duboisset, Jorge Ayllon Ugarte, Dalilia Rami, Christine Saler, Manon Reinbolt, Clara Le Fevre, Meher Ben Abdelghani, Louis-Marie Dourthe, Joffrey Perruisseau-Carrier, Marlène Nguimpi-Tambou, Flavie Barret, Luisa Di Stefano Anna, Annie Balthazard, Camille Vassord-Dang, Mathilde Le Marchand, Julien Vergniol, Iulia Pripon, Axelle Daemaegdt, Vanessa Latry, Muna Larrieu, Gaëlle Landry, Laetitia Touihri Maximin, Francesco Del Piano, Agnès Barlet, Mylène Vernisse, Sophie Lafond, Charline Genin, Camille Sibertin-Blanc, Emilien Chabrillac, Caroline Gregoire, Sébastien Vergez, Quentin Panouille, Rosine Guimbaud, Floriane Richa, Loïc Lebellec, Sophie Gounin, Guillaume Buiret, Marine Baudin, Hervé Hamon, Anne-Claire Deshorgue, Eduardo Barrascout, Stéphanie Legrand, Morgane Houlze, Linda Cambula, Anthony Lopez, Guillaume Fouquet, Kahina Touabi, Adeline GermaIn, Benoit Godbert, Florence Voivret, Julie Perrin, Rosa Da Silva, Emilie Bernichon, GCO-002 CACOVID-19 collaborators/investigators, Moulin, S., Leleu, O., Leparree, S., Goasdoue, H., Piprot, C., Tourneur, G., Bayart, V., Lignier, D., Lachaier, E., Khamari, M., Coutte, A., Siembida, N., Houessinon, A., Regimbeau, J.M., Chauffert, B., Moreira, A., Hautefeuille, V., Hee, C., Boone, M., Bihan, C., Chive, E., Poulet-Potriquier, S., Fahem, R., Luet, D., Roquin, G., Vitellius, C., Cornet-Trichereau, N., Caroli-Bosc, F.X., Thirot-Bidault, A., Ropert, S., Gachet-Masson, J., Dehais, M., L'helgoualc'h, G.A., Ali-Mahamadou, I., Talfi, S., Belmont, L., Kilendo, D., Benrezzak, N., Dubief, E., Conroy, G., Delique, L., Basso, M., Pons, I., Salignon, K., Villing, A.L., Mougenot, E., Porebski, C., Guiatni, A., Cloarec, N., Mineur, L., Bouchaud, M., David, C., Peytier, A., Greletty, T., Audemar, F., Vignes, E., Minne, F., Goldzak, G., Huysman, F., Hocine, F., Lakkis, Z., Mansi, L., Meynard, G., Almotlak, H., Klajer, E., Sun, X.S., Wasselin, J., Catala, P., Mazuy, C., Vandamme, H., Prevost, J.B., Fadin, A., Basson, L., Huguet, J.B., Dos Santos, E., Jany, B., Saad, A., Goutorbe, F., Oziol, E., Ramdani, M., Kadiri, O., Garbay, D., Huet, C., Giroux Leprieur, E., Teng, W., Monvoisin, J., Arnaud Coffin, P., Roux, S., Orfeuvre, H., Chagros, M., Pillon, D., Rassoul, A., Poureau, P.G., Novello, C., Ducray, F., Trouba, C., Bastit, V., Babin, E., Thariat, J., Leon, V., Courtecuisse, A.C., Vambre, J., Tack, V., Desauw, C., Meniai, F., Peres, C., Esparcieux, A., Perrier, H., Doux, N., Kaphan, R., Roques, B., Rebischung, C., Mille, D., Fernandes, G., Abdelli, N., Jousset, N., Combe, P., Jonveaux, E., Dumont, P., Kanaan, M., Berthelot Gras, C., Panis, V., Kaluzinski, L., Venant-Valery, M., Lam, Y.H., Vallee, L., Riviere, F., Durand, M., Benghadid, D., Villeneuve, E., Hentic Dhome, O., Laurent, L., Bounouar, Z., De Mestier, L., Dubois, J., Eyriey, M., Moreau, L., Ahle, G., Baihas, D., Aldabbagh, K., Degriffolet, D., Sebbagh, V., Seghezzi, J.C., Lozach-Brugirard, M., Mandrou, J., Mavier, L., Hennetier, F., Wagner, J.P., Carola, E., Chandirakumaran, K., Loutski, S., Cojean-Zelek, I., Bouras, A., Lacour, S., Froura, F., Ben Nadji, H., Cattelain, S., Darloy, F., Jolimoy Boilleau, G., Maissiat, C., Darut-Jouve, A., Lorgis, V., Charifi-Alaoui, I., Ghiringhelli, F., Drouillard, A., Chaix, M., Manfredi, S., Lepage, C., Gagnaire, A., Latournerie, M., Jourdan, S., Perrot, N., Folia, M., Minello, A., Jouve, J.L., Fery, M., Landau, A., Evrard, D., Valenza, B., Paitel, J.F., Chablais, L., Kreitmann, T., Lancry-Lecomte, L., Monard, A., Faugeras, E., Boucheret, P., Glommeau, C., Tchikladze, C., Garnier Tixidre, C., Long, J., Zaidi, M., Delabarre, V., Meyzenc, J., Ferrand, L., Moro-Sibilot, D., Bouheret, P., Leyronnas, C., Herve, C., Thoor, A., Jacquet, E., Roth, G., Madapathage-Senanyake, V., Chupeau, P., Bieber, E., Rosso, M., Lepage, I., Priou, F., Laly, M., Aprelon, S., Sobolak, N., Homokos, H., Pointreau, Y., Watelle, F., Pham-Becker, A., Lauridant, G., Turpin, A., Dujardin, C., Lenglin, E., Nienguet Tsota, A., Dominguez, S., Forestier, A., Nouvel, F., Lerooy, J., Ratajczak, C., Romano, O., Brzyski, D., Barriere, A., Genet, D., Tisse, J., Zasadny, X., Grelet, A., Hennion-Imbault, A., Haustraete, E., Louafi, S., Awad, M., Zekri, Y., Cheneau, C., Leissen, N., Egreteau, J., Breant, A., Sarabi, M., Labonne, S., Forestier, J., Leclercq, C., Prunier-Bossion, F., Ray Coquard, I., Guillet, M., Theillaumas, A., Prome, E., Walter, T., Philouze, P., Lawo, M., De Talhouet, S., Beuvelot, J., Molin, Y., Bellecoste Martin, M., Saussereau, M., Agnelli, L., Fakhry, N., Laplace, C., Norguet Monnereau, E., Boucard, C., Djenad, K., Fontaine, C., Seitz, J.F., Dahan, L., Sigrand, J., Duluc, M., Locher, C., Fleury, M., Brou Marie, A., Berkane, R., Poupblanc, S., Auby, D., Petran, D., Texereau, P., Guerineau, E., Andre, M., Mahjoubi, L., Sarrazin, F., Jeanson, S., Gschwend, A., Birr, V., Debieuvre, D., Fore, M., Noirclerc, M., Dahou, S., Spaeth, D., Lambotin, M., Lelu, T., Linot, B., Hugon, N., Rousseau, D., Castanie, H., Lenne, C., Lortholary, A., Cessot, A., Merzoug, M., Naudin, C., Vannetzel, J.M., Aziz, G., Hadj Arab, Y., Pernes, S., Roche-Lachaise, I., Fiteni, F., Yahiaoui, H., Marel Lopez, G., Oddoz, J., Peira, F., Michel, O., Meunier, J., Ouahrani, B., Roger, A., Branco, S., Nguyen, V., Gisselbrecht, M., Hammad, G., Mordant, P., Stroksztejn, M., Pocard, M., Nlo Meyengue, L., Aparicio, T., Sacco, E., Simon Anne, S., Fabre-Guillevin, E., Wislez, M., Slim, M., Zaanan, A., Cadranel, J., Pluvy, J., Ursu, R., Geraldo, A., Lihi, R., Vo, M., Brouk, Z., Colle, R., Bennamoun, M., Lacan, F., Louvet, C., Mebarki, S., Veyri, M., Paillaud, E., Lucas, C., Dubreuil, O., Lyamani, J., Idbaih, A., Agguini, H., Soularue, E., Canellas, A., Zalcman, G., Jourdaine, C., Verillaud, B., Herzine, H., Raymond, E., Mathiot, N., Palmieri, L.J., Epanya, C., Taieb, J., Bertrand, E., Goujon, G., Namour, C., Gazeau, B., Zafirova, B., Mirghani, H., Belin, C., Belkhir, K., Gharib, M., Vozy, A., Amrane, K., Spano, J.P., Wassermann, J., Feuvret, L., Bachet, J.B., Philonenko, S., Guillot, L., Zabbe, M., Gibiat, S., Baylot, C., Jouinot, A., Leduc, N., Vieillot, S., James, L., Ducerf, C., Blanc, J.F., Falandry Leger, C., Wautot, V., Chauvenet, M., Vincent, A., Tougeron, D., Goulvent, S., Suc, E., Laurenty, A.P., Marquis, E., Bonnaire, M., Dewolf, M., Brenet, E., Billard, D., Litre, C.F., Dumazet, A., Botsen, D., Vazel, M., Carlier, C., Bonnerave, D., Marchand-Crety, C., Bouche, O., Fosse, P., Sefrioui, D., Michel, P., Watson, S., Neuzillet, C., Torche, F., Muron, T., Natur, S., Desgrippes, R., Bihel, V., Ferrand, F.R., Leiterer, C., Lavole, J., Moquet, C., Pressoir, N., Dziukala, C., Ligeza Poisson, C., Naji, A., Williet, N., Phelip, J.M., Di Palma, F., Kherrour Mehdi, A., Langrand-Escure, J., Fournel, P., Pigne, G., Saban-Roche, L., Magne, N., Vassal, C., Jacquin, J.P., Ramirez, C., Vallard, A., Collard, O., Rivoirard, R., Graber, I., Trager Maury, S., Duboisset, E., Ayllon Ugarte, J., Rami, D., Saler, C., Reinbolt, M., Le Fevre, C., Ben Abdelghani, M., Dourthe, L.M., Perruisseau-Carrier, J., Nguimpi-Tambou, M., Barret, F., Di Stefano Anna, L., Balthazard, A., Mabro, M., Vassord-Dang, C., Le Marchand, M., Vergniol, J., Pripon, I., Daemaegdt, A., Latry, V., Larrieu, M., Landry, G., Touihri Maximin, L., Del Piano, F., Barlet, A., Vernisse, M., Lafond, S., Genin, C., Sibertin-Blanc, C., Chabrillac, E., Gregoire, C., Vergez, S., Panouille, Q., Guimbaud, R., Richa, F., Lebellec, L., Gounin, S., Buiret, G., Baudin, M., Hamon, H., Deshorgue, A.C., Barrascout, E., Legrand, S., Houlze, M., Cambula, L., Lopez, A., Fouquet, G., Touabi, K., GermaIn, A., Godbert, B., Voivret, F., Perrin, J., Da Silva, R., Bernichon, E., Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), CH Colmar, Institut Curie [Paris], Centre Hospitalier Universitaire de Reims (CHU Reims), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Beaujon, Hôpital Foch [Suresnes], CHU Saint-Antoine [AP-HP], ARCAGY-GINECO, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut Gustave Roussy (IGR), Département de médecine nucléaire [Rennes], CRLCC Eugène Marquis (CRLCC), Département de médecine oncologique [Gustave Roussy], Département de cancérologie cervico-faciale [Gustave Roussy] (CCF), Centre Jean Bernard [Institut Inter-régional de Cancérologie - Le Mans], Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hopital Saint-Louis [AP-HP] (AP-HP), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), AbbVie, Merck, Carthera, Transgene, Nutritheragene, Roche, Air Liquide, Eli Lilly Japan, LEO Pharma Research Foundation, Bayer, Novartis, Sanofi, Biogen, Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, 0301 basic medicine, Cancer Research, medicine.medical_treatment, Disease, law.invention, Cohort Studies, 0302 clinical medicine, Mechanical ventilation, Risk Factors, law, Neoplasms, Medicine, Prospective Studies, Prospective cohort study, Original Research, Cancer, Intensive care unit, 3. Good health, Death, Oncology, 030220 oncology & carcinogenesis, Female, France, Immunotherapy, Cohort study, medicine.medical_specialty, chemotherapy. radiotherapy, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Internal medicine, Humans, Chemotherapy, Mortality, Pandemics, Aged, Retrospective Studies, Radiotherapy, SARS-CoV-2, business.industry, COVID-19, Retrospective cohort study, Odds ratio, medicine.disease, Antineoplastic Agents/adverse effects, Antineoplastic Agents/therapeutic use, COVID-19/mortality, France/epidemiology, Neoplasms/mortality, Neoplasms/therapy, Neoplasms/virology, SARS-CoV-2/isolation & purification, 030104 developmental biology, business
Abstract: Background Cancer patients are thought to have an increased risk of developing severe Coronavirus Disease 2019 (COVID-19) infection and of dying from the disease. In this work, predictive factors for COVID-19 severity and mortality in cancer patients were investigated. Patients and Methods In this large nationwide retro-prospective cohort study, we collected data on patients with solid tumours and COVID-19 diagnosed between March 1 and June 11, 2020. The primary endpoint was all-cause mortality and COVID-19 severity, defined as admission to an intensive care unit (ICU) and/or mechanical ventilation and/or death, was one of the secondary endpoints. Results From April 4 to June 11, 2020, 1289 patients were analysed. The most frequent cancers were digestive and thoracic. Altogether, 424 (33%) patients had a severe form of COVID-19 and 370 (29%) patients died. In multivariate analysis, independent factors associated with death were male sex (odds ratio 1.73, 95%CI: 1.18-2.52), ECOG PS ≥ 2 (OR 3.23, 95%CI: 2.27-4.61), updated Charlson comorbidity index (OR 1.08, 95%CI: 1.01-1.16) and admission to ICU (OR 3.62, 95%CI 2.14-6.11). The same factors, age along with corticosteroids before COVID-19 diagnosis, and thoracic primary tumour site were independently associated with COVID-19 severity. None of the anticancer treatments administered within the previous 3 months had any effect on mortality or COVID-19 severity, except cytotoxic chemotherapy in the subgroup of patients with detectable SARS-CoV-2 by RT-PCR, which was associated with a slight increase of the risk of death (OR 1.53; 95%CI: 1.00-2.34; p = 0.05). A total of 431 (39%) patients had their systemic anticancer treatment interrupted or stopped following diagnosis of COVID-19. Conclusions Mortality and COVID-19 severity in cancer patients are high and are associated with general characteristics of patients. We found no deleterious effects of recent anticancer treatments, except for cytotoxic chemotherapy in the RT-PCR-confirmed subgroup of patients. In almost 40% of patients, the systemic anticancer therapy was interrupted or stopped after COVID-19 diagnosis., Highlights • A total of 1289 patients with solid tumours and COVID-19 were analysed. • Mortality and COVID-19 severity were mainly driven by patient general characteristics. • Overall, we found no deleterious effects of recent anticancer treatments on mortality. . • Systemic anticancer treatment was interrupted or stopped in 39% of patients.
Published: 2020

46. Formal approaches to the study of parliaments

Author: Cesar Garcia Perez de Leon and Patrick Dumont
Published: 2020

47. Weekly paclitaxel plus bevacizumab versus docetaxel as second- or third-line treatment in advanced non-squamous non-small-cell lung cancer: Results of the IFCT-1103 ULTIMATE study

Author: Olivier Raffy, Adrien Dixmier, Gérard Zalcman, Clara Fontaine-Delaruelle, Damien Pouessel, Olivier Molinier, Sandrine Hiret, Franck Morin, Patrick-Aldo Renault, Julien Mazieres, Charles Dayen, Patrick Dumont, Catherine Becht, Sylvestre Le Moulec, Eric Pichon, Benjamin Besse, Clarisse Audigier-Valette, Claire Poulet, Fabrice Barlesi, Alexis B. Cortot, Denis Moro-Sibilot, and Alexandra Langlais
Subjects: 0301 basic medicine, Adult, Male, Cancer Research, medicine.medical_specialty, Lung Neoplasms, Bevacizumab, Adolescent, Paclitaxel, medicine.medical_treatment, Population, Docetaxel, Kaplan-Meier Estimate, Neutropenia, Gastroenterology, Drug Administration Schedule, 03 medical and health sciences, chemistry.chemical_compound, Young Adult, 0302 clinical medicine, Internal medicine, Carcinoma, Non-Small-Cell Lung, Antineoplastic Combined Chemotherapy Protocols, Medicine, Humans, Lung cancer, education, Aged, Neoplasm Staging, Aged, 80 and over, Chemotherapy, education.field_of_study, Cross-Over Studies, business.industry, Hazard ratio, Middle Aged, medicine.disease, Progression-Free Survival, 030104 developmental biology, Oncology, chemistry, 030220 oncology & carcinogenesis, Disease Progression, Female, business, medicine.drug
Abstract: Purpose Second-line chemotherapy regimens have demonstrated poor benefit after failure of platinum-based chemotherapy in advanced non-squamous non–small-cell lung cancer (nsNSCLC). Methods In this multicentre, open-label phase III trial, patients with advanced nsNSCLC treated with one or two prior lines, including one platinum-based doublet, were centrally randomised to receive 90 mg/m2 of paclitaxel (D1, D8, D15) plus 10 mg/kg of bevacizumab (D1, D15) every 28 days or docetaxel (75 mg/m2) every 21 days; crossover was allowed after disease progression. Primary end-point was progression-free survival (PFS). ClinicalTrials.gov registration number: NCT01763671 . Results One hundred sixty six patients were randomised (paclitaxel plus bevacizumab: 111, docetaxel: 55). The median PFS was longer in patients receiving paclitaxel plus bevacizumab than in patients receveing docetaxel [5·4 months versus 3·9 months, adjusted hazard ratio (HR) 0·61 (95% confidence interval [CI]: 0·44–0·86); p = 0·005]. Objective response rates (ORRs) were 22·5% (95% CI: 14·8–30·3) and 5·5% (95% CI: 0·0–11·5) (p = 0·006), respectively. Median overall survivals were similar (adjusted HR 1·17; p = 0·50). Crossover occurred in 21 of 55 (38·2%) docetaxel-treated patients. Grade III-IV adverse events (AEs) were reported in 45·9% and 54·5% of patients treated with paclitaxel and bevacizumab or docetaxel, respectively (p = NS), including neutropenia (19·3% versus 45·4%), neuropathy (8·3% versus 0·0%) and hypertension (7·3% versus 0·0%). Three patients died due to treatment-related AEs (1·8% in each group). Conclusion Weekly paclitaxel plus bevacizumab as second- or third-line improves PFS and ORR compared with docetaxel in patients with nsNSCLC, with an acceptable safety profile. These results place weekly paclitaxel plus bevacizumab as a valid option in this population. Clinical trials registration number ClinicalTrials.gov Identifier: NCT01763671 .
Published: 2020

48. Luxembourg: Political development and data for 2017

Author: Raphaël Kies and Patrick Dumont
Subjects: Politics, Political economy, Political science, 0502 economics and business, 05 social sciences, 050602 political science & public administration, 050207 economics, 0506 political science
Published: 2018

49. Serine 392 phosphorylation modulates p53 mitochondrial translocation and transcription-independent apoptosis

Author: Patrick Dumont, Cédric Castrogiovanni, Béranger Waterschoot, and Olivier De Backer
Subjects: 0301 basic medicine, Transcription, Genetic, Mutant, Apoptosis Regulatory Proteins/metabolism, Apoptosis, Mitochondria/chemistry, Mitochondrion, Serine, 03 medical and health sciences, Genetic, Humans, Phosphorylation, Molecular Biology, Transcription factor, Protein Processing, Serine/metabolism, Original Paper, biology, Chemistry, Cytochrome c, Post-Translational, Cell Biology, Mitochondria, Cell biology, Camptothecin/toxicity, Protein Transport, 030104 developmental biology, HtrA serine peptidase 2, Tumor Suppressor Protein p53/chemistry, Mutation, biology.protein, Camptothecin, Tumor Suppressor Protein p53, CRISPR-Cas Systems, Apoptosis Regulatory Proteins, Protein Processing, Post-Translational, Transcription
Abstract: The tumor suppressor p53 is a key regulator of apoptosis induced by various cellular stresses. p53 can induce apoptosis by two mechanisms. First, p53 acts as a transcription factor inducing and repressing pro-apoptotic and anti-apoptotic targets genes, respectively. Second, p53 is able to translocate to the mitochondria, where it interacts with BCL-2 family members to induce membrane permeabilization and cytochrome c release. p53 transcriptional activity is regulated by a set of post-translational modifications that have been well documented. However, how these modifications impact the direct mitochondrial pathway of death remain poorly understood. In this study, we focused on the role of serine 392 phosphorylation in the control of p53-dependent apoptosis. We used CRISPR/Cas9 genome editing to substitute serine 392 by a non-phosphorylatable alanine in HCT-116 colon carcinoma cells. The S392A mutant displayed normal transcriptional activity following genotoxic stress, but markedly impaired ability to localize to mitochondria. The decreased mitochondrial localization of the S392A mutant correlated with a lower ability to induce apoptosis. Confirmatory observations were made following enforced expression of the S392A p53 mutant or a phospho-mimetic S392E mutant in H1299 lung carcinoma cells. Our observations support the premise that serine 392 phosphorylation of p53 influences its mitochondrial translocation and transcription-independent apoptotic function.
Published: 2018

50. Party Politics in European Microstates

Author: Fernando Casal Bértoa, Patrick Dumont, Fernando Casal Bértoa, and Patrick Dumont
Subjects: Political parties--Europe, Political culture--Europe, States, Small--Politics and government
Abstract: This book represents the first comprehensive study of the evolution of parties and party systems in all nine democratic European states with less than one million inhabitants.As small political units have for long been considered to be most conducive to stable democracy, this volume analyses the actual role of political parties and partisan competition in the operation of modern democracy in those European microstates. Drawing on the crucial contribution of leading country experts in the field, it provides rich, systematic contextualized knowledge on these lesser-known cases. It further contributes to the mainstreaming of small state research in social science studies by comparing the experience of party politics in European microstates with that of larger countries in the same region of the world.This volume will be of key interest to scholars and students of party systems and political parties, elections and democracy, small states, European politics and more broadly of comparative politics.
Published: 2022

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